Denticleless E3 ubiquitin protein ligase (DTL) maintains the proliferation and differentiation of epidermis and hair follicles during skin development.

BACKGROUND: A precise balance between the proliferation and differentiation of epidermal progenitors is required to achieve the barrier function during the development of epidermis. During the entire process of skin development, the newly formed basal layer cells divide, differentiate, and migrate outward to the surface of the skin, which is tightly regulated by a series of events related to cell cycle progression. The CRL4DTL complex (Cullin 4 RING ligase, in association with the substrate receptor DTL) has long emerged as a master regulator in various cellular processes, which mediates the degradation of key cell cycle proteins. However, the roles of DTL in regulating epidermal morphogenesis during skin development remain unclear. RESULTS: We showed that DTL deficiency in epidermal progenitor cells leads to defects in epidermal stratification and loss of hair follicles accompanied by reduced epidermal progenitor cells and disturbed cell cycle progression during skin development. Transcriptome analysis revealed that p53 pathway is activated in DTL-depleted epidermal progenitor cells. The apoptosis of epidermal cells showed in DTL deficiency mice is rescued by the absence of p53, but the proliferation and differentiation defects were p53-independent. CONCLUSION: Our findings indicate that DTL plays a vital role in epidermal malformation during skin development.

Children's oppositional defiant disorder symptoms and neural synchrony in mother-child interactions: An fNIRS study.

Interpersonal neural synchrony (INS) between mothers and children responds to the temporal similarity of brain signals in joint behavior between dyadic partners and is considered an important neural indicator of the formation of adaptive social interaction bonds. Parent-child interactions are particularly important for the development and maintenance of oppositional defiant disorder (ODD) in children, but the underlying neurocognitive mechanisms are unknown. Therefore, in the current study we measured INS between mothers and children in interactions by using simultaneous functional Near-infrared Spectroscopy (fNIRS), and explored its association with ODD symptoms in children. Seventy-two mother-child dyads were recruited to participate in the study, including 35 children with ODD and 37 healthy children to be used as a control. Each mother-child dyad was measured for neural activity in frontal, parietal, and temporal lobe regions while completing free-play as well as positive, and negative topic discussion tasks. We used Phase-locked value to calculate the synchrony strength and then used the K-means algorithm and k-space based alignment tests to confirm the specific patterns of parent-child synchrony in different brain areas. The results showed that, in free-play (right MFG and bilateral SFG), positive (left TPJ and bilateral SFGdor), and negative (bilateral SFGmed, right ANG, and left MFG) topic discussions, the mother-child pairs showed different patterns of INS. These specific INS patterns were significantly lower in the ODD group compared to the control group and were negatively associated with ODD symptoms in children. Network analyses showed that these INS patterns were connected to different nodes in the ODD symptom network. Our findings suggest that ODD mother-child dyads exhibit lower neural synchrony across a wide range of parent-child interactions. Neural synchrony in the context of interpersonal interactions provides new insights into understanding the neural mechanisms of ODD and can be used as an indicator of neural and socio-environmental factors in the network of psychological disorder symptoms.

Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era.

INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis.

The long-term high-fat diet (HFD) can cause myocardial lipotoxicity, which is characterized pathologically by myocardial hypertrophy, fibrosis, and remodeling and clinically by cardiac dysfunction and heart failure in patients with obesity and diabetes. Circular RNAs (circRNAs), a novel class of noncoding RNA characterized by a ring formation through covalent bonds, play a critical role in various cardiovascular diseases. However, few studies have been conducted to investigate the role and mechanism of circRNA in myocardial lipotoxicity. Here, we found that circ_005077, formed by exon 2-4 of Crmp1, was significantly upregulated in the myocardium of an HFD-fed rat. Furthermore, we identified circ_005077 as a novel ferroptosis-related regulator that plays a role in palmitic acid (PA) and HFD-induced myocardial lipotoxicity in vitro and in vivo. Mechanically, circ_005077 interacted with Cyclophilin A (CyPA) and inhibited its degradation via the ubiquitination proteasome system (UBS), thus promoting the interaction between CyPA and p47phox to enhance the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase responsible for ROS generation, subsequently inducing ferroptosis. Therefore, our results provide new insights into the mechanisms of myocardial lipotoxicity, potentially leading to the identification of a novel therapeutic target for the treatment of myocardial lipotoxicity in the future.

High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes.

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

Machine learning-based QSAR and LB-PaCS-MD guided design of SARS-CoV-2 main protease inhibitors.

The global outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 virus had led to profound respiratory health implications. This study focused on designing organoselenium-based inhibitors targeting the SARS-CoV-2 main protease (Mpro). The ligand-binding pathway sampling method based on parallel cascade selection molecular dynamics (LB-PaCS-MD) simulations was employed to elucidate plausible paths and conformations of ebselen, a synthetic organoselenium drug, within the Mpro catalytic site. Ebselen effectively engaged the active site, adopting proximity to H41 and interacting through the benzoisoselenazole ring in a π-π T-shaped arrangement, with an additional π-sulfur interaction with C145. In addition, the ligand-based drug design using the QSAR with GFA-MLR, RF, and ANN models were employed for biological activity prediction. The QSAR-ANN model showed robust statistical performance, with an r2training exceeding 0.98 and an RMSEtest of 0.21, indicating its suitability for predicting biological activities. Integration the ANN model with the LB-PaCS-MD insights enabled the rational design of novel compounds anchored in the ebselen core structure, identifying promising candidates with favorable predicted IC50 values. The designed compounds exhibited suitable drug-like characteristics and adopted an active conformation similar to ebselen, inhibiting Mpro function. These findings represent a synergistic approach merging ligand and structure-based drug design; with the potential to guide experimental synthesis and enzyme assay testing.

Mechanistic and therapeutic perspectives of non-coding RNA-modulated apoptotic signaling in diabetic retinopathy.

Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.

High-performance liquid chromatography analysis of alkaloids in various parts of lotus extracts with ion mobility spectrometry and mass spectrometry dual detection.

Using high-performance liquid chromatography coupled with electrospray ionization-ion mobility spectrometry and mass spectrometry, we proposed a dual-detection method for the identification and profiling of alkaloids in various lotus parts including leaf, plumule, stem, seed epicarp, and receptacle. The eluent from high-performance liquid chromatography was split and conducted to electrospray ionization-ion mobility spectrometry and time-of-flight mass spectrometry separately to facilitate the compound identification. In total, 23 kinds of alkaloids were identified based on m/z, drift time, and retention time, including alkaloid isomers such as lirinidine, N-nornuciferine, and O-nornuciferine with identical m/z that are difficult to differentiate using mass spectrometry alone. Using this method, we investigated the changing dynamics of alkaloid accumulation in lotus leaves and lotus stems at different harvesting periods. The total alkaloid content showed an increasing trend with the growth and development of leave and stem. Overall, the developed dual detection method has the advantages of high peak capacity and high sensitivity compared with the conventional detection method and facilitates the identification of detected compounds.

Hemoadsorption and Coagulation Systemic Rebalance in Patients Undergoing Nonelective Cardiac Surgery and Treated with Antithrombotics.

INTRODUCTION: Insufficient withdrawal duration of antithrombotics leads to excessive bleeding after major surgery. We hypothesize that intraoperative hemoadsorption (HA) can reduce postoperative allogeneic transfusion requirements and excessive bleeding events (EBE), without an increase in ischemic/thromboembolic events (ITE) in patients who have taken antithrombotics and undergone nonelective cardiac surgery. METHODS: A total of 460 patients admitted to our hospital from 2018 to 2022 were included in this study and divided into two groups: HA and non-HA. Because of the risk of bias due to differences in antithrombotic type, withdrawal duration, or basic coagulation function, propensity score matching was used for analyses. RESULTS: Out of 154 cases in the HA group, 144 pairs were successfully matched. No HA safety events such as hemolysis, hypotension, or device failure occurred. After matching, the two groups were found to be comparable in preoperative antithrombotic type, withdrawal duration, platelets and coagulation function, and demographic and perioperative characteristics. Although the HA group did not have a reduced incidence of EBE, this group exhibited significant decreases in the transfusion rate and volume, the incidence of ITE, acute kidney injury, and central nervous system injury. CONCLUSIONS: For patients who have undergone nonelective cardiac surgery and taken antithrombotics, HA can simply and safely rebalance the postoperative coagulation system and have associations with reduced transfusion and postoperative ITE.

Transfer-printed, tandem microscale light-emitting diodes for full-color displays.

Inorganic semiconductor-based microscale light-emitting diodes (micro-LEDs) have been widely considered the key solution to next-generation, ubiquitous lighting and display systems, with their efficiency, brightness, contrast, stability, and dynamic response superior to liquid crystal or organic-based counterparts. However, the reduction of micro-LED sizes leads to the deteriorated device performance and increased difficulties in manufacturing. Here, we report a tandem device scheme based on stacked red, green, and blue (RGB) micro-LEDs, for the realization of full-color lighting and displays. Thin-film micro-LEDs (size ∼100 µm, thickness ∼5 µm) based on III-V compound semiconductors are vertically assembled via epitaxial liftoff and transfer printing. A thin-film dielectric-based optical filter serves as a wavelength-selective interface for performance enhancement. Furthermore, we prototype arrays of tandem RGB micro-LEDs and demonstrate display capabilities. These materials and device strategies provide a viable path to advanced lighting and display systems.

Direct Photo-Patterning of Efficient and Stable Quantum Dot Light-Emitting Diodes via Light-Triggered, Carbocation-Enabled Ligand Stripping.

Next generation displays based on quantum dot light-emitting diodes (QLEDs) require robust patterning methods for quantum dot layers. However, existing patterning methods mostly yield QLEDs with performance far inferior to the state-of-the-art individual devices. Here, we report a light-triggered, carbocation-enabled ligand stripping (CELS) approach to pattern QLEDs with high efficiency and stability. During CELS, photogenerated carbocations from triphenylmethyl chlorides remove native ligands of quantum dots, thereby producing patterns at microscale precision. Chloride anions passivate surface defects and endow patterned quantum dots with preserved photoluminescent quantum yields. It works for both cadmium-based and heavy-metal-free quantum dots. CELS-patterned QLEDs show remarkable external quantum efficiencies (19.1%, 17.5%, 12.0% for red, green, blue, respectively) and a long operation lifetime (T95 at 1000 nits up to 8700 h). Both are among the highest for patterned QLEDs and approach the records for nonpatterned devices, which makes CELS promising for building high-performance QLED displays and related integrated devices.

Boosting Blue Self-Trapped Exciton Emission in All-Inorganic Zero-Dimensional Metal Halide Cs2ZnCl4 via Zirconium (IV) Doping.

Low-dimensional metal halides with efficient luminescence properties have received widespread attention recently. However, nontoxic and stable low-dimensional metal halides with efficient blue emission are rarely reported. We used a solvothermal synthesis method to synthesize tetravalent zirconium ion-doped all-inorganic zero-dimensional Cs2ZnCl4 for the first time. Bright blue emission in the range of 370 nm-700 nm with a emission maximum at 456 nm was observed in Zr4+:Cs2ZnCl4 accompanied by a large Stokes shift, which was due to self-trapped excitons (STEs) caused by the lattice vibrations of the twisted structure. Simultaneously, the PLQY of Zr4+:Cs2ZnCl4 achieve an impressive 89.67%, positioning it as a compelling contender for future applications in blue-light technology.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy.

Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia. Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events. Results The study population consisted of 24 cases of insulinoma patients, 7 males and 17 females, aged 46.08±14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51±3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 (interquartile range [IQR]: 2.50-2.90) mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P < 0.001]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P < 0.001). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P < 0.001], but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose. Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Carbonyl- and Nitrogen-Embedded Multi-Resonance Emitter with Ultra-Pure Green Emission and High Electroluminescence Efficiencies.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) emitters with narrow emission spectra have garnered significant attention in future organic light-emitting diode (OLED) displays. However, current C=O/N-embedded MR-TADF systems still lack satisfactory performance in terms of electroluminescence bandwidths and external quantum efficiencies (EQEs). In this study, a C=O/N-embedded green MR-TADF emitter, featuring two acridone units incorporated in a sterically protected 11-ring fused core skeleton, is successfully synthesized through finely controlling the reaction selectivity. The superior combination of multiple intramolecular fusion and steric wrapping strategies in the design of the emitter not only imparts an extremely narrow emission spectrum and a high fluorescence quantum yield to the emitter but also mitigates aggregation-induced spectral broadening and fluorescence quenching. Therefore, the emitter exhibits leading green OLED performance among C=O/N-based MR-TADF systems, achieving an EQE of up to 37.2 %, a full width at half maximum of merely 0.11 eV (24 nm), and a Commission Internationale de l'Éclairage coordinate of (0.20, 0.73). This study marks a significant advance in the realization of ideal C=O/N-based MR-TADF emitters and holds profound implications for the design and synthesis of other MR-TADF systems.

Precise Regulation of Multiple Resonance Distribution Regions of a B,N-Embedded Polycyclic Aromatic Hydrocarbon to Customize Its BT2020 Green Emission.

Recently, boron (B)/nitrogen (N)-embedded polycyclic aromatic hydrocarbons (PAHs), characterized by multiple resonances (MR), have attracted significant attention owing to their remarkable features of efficient narrowband emissions with small full width at half maxima (FWHMs). However, developing ultra-narrowband pure-green emitters that comply with the Broadcast Service Television 2020 (BT2020) standard remains challenging. Precise regulation of the MR distribution regions allows simultaneously achieving the emission maximum, FWHM value, and spectral shape that satisfy the BT2020 standard. The proof-of-concept molecule TPABO-DICz exhibited ultrapure green emission with a dominant peak at 515 nm, an extremely small FWHM of 17 nm, and Commission Internationale de l'Eclairage (CIE) coordinates of (0.17, 0.76). The corresponding bottom-emitting organic light-emitting diode (OLED) exhibited a remarkably high CIEy value (0.74) and maximum external quantum efficiency (25.8 %). Notably, the top-emitting OLED achieved nearly BT2020 green color (CIE: 0.14, 0.79) and exhibited a state-of-the-art maximum current efficiency of 226.4 cd A-1 , thus fully confirming the effectiveness of the above strategy.

TREM2 expression promotes liver and peritoneal M2 macrophage polarization in mice infected with Schistosoma japonicum.

Schistosomiasis is a tropical parasitic disease that damages the liver and poses a serious threat to human health. Macrophages play a key role in the development of liver granulomas and fibrosis by undergoing polarization from M1 to M2 type during schistosomiasis. Therefore, regulating macrophage polarization is important for controlling pathological changes that occur during this disease. Triggering receptor expressed on myeloid cells 2 (TREM2) expressed on the surface of macrophages, dendritic cells and other immune cells has been shown to play a role in inhibiting inflammatory responses and regulating M2 macrophage polarization, however its role in macrophage polarization in schistosomiasis has not been investigated. In this study, we confirmed that TREM2 expression was upregulated in the livers and peritoneal macrophages of mice infected with Schistosoma japonicum. Moreover, the TREM2 expression trend correlated with the expression of M2 macrophage polarization-related molecules in the liver tissues of S. japonicum-infected mice. Using Trem2-/- mice, we also showed that Trem2 deletion inhibited Arg1 and Ym1 expression in liver tissues. Trem2 deletion also increased the number of F4/80 + CD86+ cells in peritoneal macrophages of infected mice. In summary, our study suggests that TREM2 may be involved in M2 macrophage polarization during schistosomiasis.

Identification of UBFD1 as a prognostic biomarker and molecular target among estrogen receptor-positive breast cancer.

Estrogen receptor (ER)-positive breast cancer (BRCA) is the most commonly diagnosed molecular subtype of BRCA. It is routinely treated with endocrine therapy; however, some patients relapse after therapy and develop drug resistance, resulting in treatment failure. In the present study, we identified markers of ER-positive BRCA and evaluated their putative function in immune infiltration as well as their clinicopathological significance. The ubiquitin family domain containing 1 (UBFD1) protein was associated with the prognosis of ER-positive BRCA patients. Its expression was higher in ER-positive BRCA tissues compared with adjacent nontumor tissues. Patients with higher UBFD1 expression had a poorer prognosis. UBFD1 is an independent risk factor for ER-positive BRCA patients and its function was primarily associated with hormone activity and inflammation. Taken together, UBFD1 is a potential prognostic biomarker and candidate target of ER-positive BRCA.

Automatic elimination of phase aberrations in digital holography based on Gaussian 1σ- criterion and histogram segmentation.

We propose a numerical and automatic quadratic phase aberration elimination method in digital holography for phase-contrast imaging. A histogram segmentation method based on Gaussian 1σ-criterion is used to obtain the accurate coefficients of quadratic aberrations using the weighted least-squares algorithm. This method needs no manual intervention for specimen-free zone or prior parameters of optical components. We also propose a maximum-minimum-average-standard deviation (MMASD) metric to quantitatively evaluate the effectiveness of quadratic aberration elimination. Simulation and experimental results are demonstrated to verify the efficacy of our proposed method over the traditional least-squares algorithm.

Characteristics and response cutoff of octreotide suppression test in thyrotrophin (TSH)-secreting pituitary adenomas.

CONTEXT: Somatostatin analogs are recommended for preoperative therapy in thyrotrophin secreting pituitary adenomas (TSHomas). Octreotide suppression test (OST) was designed to differentiate TSHomas with resistance to thyroid hormones, while its ability to test the sensitivity of SSA has not been fully studied. OBJECTIVE: To test the sensitivity of SSA in TSHomas with OST. PATIENTS: We collected 48 pathologically confirmed TSHoma patients with complete 72 h' data of OST into analysis. INTERVENTION: Octreotide suppression test. MAIN OUTCOME: Sensitivity timepoint and cutoff of OST. RESULTS: During the entire OST, the TSH descended maximally 89.07% (73.85%, 96.77%), while the FT3 and FT4 declined slowly [43.40% (37.80%, 54.44%) and 26.59% (19.01%, 33.13%), respectively]. The 24th hour was the timepoint wherein the stability occurs for TSH, and the 48th hour for FT3 and FT4 during OST. In the patients who received both short- and long-acting somatostatin analogs (SSA), the 24-h timepoint was the most predictive timepoint for the percentage of TSH decline (Spearman's rank correlation analysis, r = .571, p < .001), while the 72-h timepoint was optimal for predicting the magnitude of TSH decline (Spearman's rank correlation analysis, r = .438, p = .005). In the 24th timepoint, a positive correlation was also observed between TSH suppression rate and the percentage decrease and absolute value decrease of FT3 and FT4. Furthermore, in patients treated with long-acting SSA, the 72-h timepoint was optimal for predicting both the percentage (Spearman's rank correlation analysis, r = .587, p = .01) and magnitude (Spearman's rank correlation analysis, r = .474, p = .047) of TSH decline. The 24th hour was the optimal timepoint with 44.54% (50% of median value of TSH in 72-hOST) decrease of TSH being the observing cutoff. The adverse effect of OST was predominantly occurred in the gastrointestinal system and no severe event occurred during OST. Paradoxical response could occur in OST and it did not influence the effect of SSA as long as sensitivity was confirmed. A high level of hormonal control was achieved in the SSA-sensitive patients. CONCLUSION: OST can be used as an efficient tool to guide the adequate use of SSA.